{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:57:35Z","timestamp":1777395455678,"version":"3.51.4"},"reference-count":35,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,5,17]]},"abstract":"<jats:p>Background: Modulation of serotonergic signaling by treatment with selective serotonin reuptake inhibitors (SSRIs) has been suggested to mitigate amyloid-\u03b2 (A\u03b2) pathology in Alzheimer\u2019s disease, in addition to exerting an anti-depressant action. Objective: To investigate the efficacy of chronic treatment with the SSRI paroxetine, in mitigating A\u03b2 pathology and A\u03b2 plaque-induced microgliosis in the hippocampus of 18-month-old APPswe\/PS1\u0394E9 mice. Methods: Plaque-bearing APPswe\/PS1\u0394E9 and wildtype mice were treated with paroxetine per os at a dose of 5\u200amg\/kg\/day, from 9 to 18 months of age. The per os treatment was monitored by recording of the body weights and serum paroxetine concentrations, and by assessment of the serotonin transporter occupancy by [3H]DASB-binding in wildtype mice. Additionally, 5,7-dihydroxytryptamine was administered to 9-month-old APPswe\/PS1\u0394E9 mice, to examine the effect of serotonin depletion on A\u03b2 pathology. A\u03b2 pathology was evaluated by A\u03b2 plaque load estimation and the A\u03b242\/A\u03b240 ratio by ELISA. Results: Paroxetine treatment led to &gt;\u200a80% serotonin transporter occupancy. The treatment increased the body weight of wildtype mice, but not of APPswe\/PS1\u0394E9 mice. The treatment had no effect on the A\u03b2 plaque load (p\u200a=\u200a0.39), the number and size of plaques, or the A\u03b2 plaque-induced increases in microglial numbers in the dentate gyrus. Three months of serotonin depletion did not significantly impact the A\u03b2 plaque load or A\u03b242\/A\u03b240 ratio in APPswe\/PS1\u0394E9 mice at 12 months. Conclusion: Our results show that chronic treatment with the SSRI paroxetine does not mitigate A\u03b2 pathology and A\u03b2 plaque-induced microgliosis in the hippocampus of APPswe\/PS1\u0394E9 mice.<\/jats:p>","DOI":"10.3233\/jad-220019","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T18:24:12Z","timestamp":1647973452000},"page":"685-699","source":"Crossref","is-referenced-by-count":9,"title":["Efficacy of Chronic Paroxetine Treatment in Mitigating Amyloid Pathology and Microgliosis in APPSWE\/PS1\u0394E9 Transgenic Mice"],"prefix":"10.1177","volume":"87","author":[{"given":"Mithula","family":"Sivasaravanaparan","sequence":"first","affiliation":[{"name":"Department of Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise \u00d8rum","family":"Olesen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Aarhus 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